Brush copolymers

ABSTRACT

Brush copolymers containing (a) monomeric units derived from an ethylenically unsaturated-containing monomer containing one or more boronic acid moieties; and (b) monomeric units derived from an ethylenically unsaturated-containing macromonomer having hydrophilic units and boronic acid units are disclosed.

This application is a continuation of U.S. patent application Ser. No.12/641,490 filed on Dec. 18, 2009 and claims the benefit of ProvisionalPatent Application No. 61/203,882 filed Dec. 30, 2008 the contents ofeach of which are incorporated by reference herein.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention generally relates to a brush copolymer and abiomedical device such as an ophthalmic lens having a brush copolymercoating on at least a portion of a surface thereof.

2. Description of Related Art

Medical devices such as ophthalmic lenses made from, for example,silicone-containing materials, have been investigated for a number ofyears. Such materials can generally be subdivided into two majorclasses, namely, hydrogels and non-hydrogels. Hydrogels can absorb andretain water in an equilibrium state, whereas non-hydrogels do notabsorb appreciable amounts of water. Regardless of their water content,both hydrogel and non-hydrogel silicone medical devices tend to haverelatively hydrophobic, non-wettable surfaces that have a high affinityfor lipids. This problem is of particular concern with contact lenses.

Those skilled in the art have long recognized the need for modifying thesurface of such silicone contact lenses so that they are compatible withthe eye. It is known that increased hydrophilicity of the lens surfaceimproves the wettability of the contact lens. This, in turn, isassociated with improved wear comfort of contact lenses. Additionally,the surface of the lens can affect the lens's susceptibility todeposition, particularly the deposition of proteins and lipids resultingfrom tear fluid during lens wear. Accumulated deposition can cause eyediscomfort or even inflammation. In the case of extended wear lenses(i.e., lenses used without daily removal of the lens before sleep), thesurface is especially important, since extended wear lenses must bedesigned for high standards of comfort and biocompatibility over anextended period of time.

Silicone lenses have been subjected to plasma surface treatment toimprove their surface properties, e.g., surfaces have been rendered morehydrophilic, deposit resistant, scratch-resistant, or otherwisemodified. Examples of previously disclosed plasma surface treatmentsinclude subjecting the surface of a contact lens to a plasma containingan inert gas or oxygen (see, for example, U.S. Pat. Nos. 4,055,378;4,122,942; and 4,214,014); various hydrocarbon monomers (see, forexample, U.S. Pat. No. 4,143,949); and combinations of oxidizing agentsand hydrocarbons such as water and ethanol (see, for example, WO95/04609 and U.S. Pat. No. 4,632,844). U.S. Pat. No. 4,312,575 disclosesa process for providing a barrier coating on a silicone or polyurethanelens by subjecting the lens to an electrical glow discharge (plasma)process conducted by first subjecting the lens to a hydrocarbonatmosphere followed by subjecting the lens to oxygen during flowdischarge, thereby increasing the hydrophilicity of the lens surface.

U.S. Pat. No. 6,582,754 (“the '754 patent”) discloses a process forcoating a material surface involving the steps of (a) providing anorganic bulk material having functional groups on its surface; (b)covalently binding to the surface of the bulk material a layer of afirst compound having a first reactive group and an ethylenicallyunsaturated double bond by reacting the function groups on the surfaceof the bulk material with the first reactive group of the firstcompound; (c) copolymerizing, on the surface of the bulk material, afirst hydrophilic monomer and a monomer comprising a second reactivegroup to form a coating comprising a plurality of primary polymer chainswhich are covalently bonded to the surface through the first compound,wherein each primary polymer chain comprises second reactive; (d)reacting the second reactive groups of the primary polymer chains with asecond compound comprising an ethylenically unsaturated double bond anda third reactive group that is co-reactive with the second reactivegroup, to covalently bind the second compound to the primary polymerchains; and (e) graft-polymerizing a second hydrophilic monomer toobtain a branched hydrophilic coating on the surface of the bulkmaterial, wherein the branched hydrophilic coating comprises theplurality of the primary polymer chains and a plurality of secondarychains each of which is covalently attached through the second compoundto one of the primary chains. The process disclosed in the '754 patentis time consuming as it involves multiple steps and uses many reagentsin producing the coating on the substrate.

Blister packages and glass vials are typically used to individuallypackage each soft contact lens for sale to a customer. Saline ordeionized water is commonly used to store the lens in the packages, asmentioned in various patents related to the packaging or manufacturingof contact lenses. Because lens material may tend to stick to itself andto the lens package, packaging solutions for blister packs havesometimes been formulated to reduce or eliminate lens folding andsticking; packaging solutions may include a polymer to improve comfortof the contact lens. Polyvinyl alcohol (PVA) has been used in contactlens packaging solutions. Additionally, U.S. Pat. No. 6,440,366discloses contact lens packaging solutions comprising polyethylene oxide(PEO)/polypropylene oxide (PPO) block copolymers, especially poloxamersor poloxamines.

U.S. Patent Application Publication No. 20080151181 (“the '181application), commonly assigned to assignee herein Bausch & LombIncorporated, discloses a contact lens having its surfaces coated withan inner layer and an outer layer, the inner layer comprising a polymercomprising monomeric units derived from an ethylenically unsaturatedmonomer containing a boronic acid moiety, and the outer layer comprisinga diol. The '181 application further discloses that the diol layerincludes at least one diol-terminated polymer member selected from thegroup consisting of diol-terminated polyvinyl pyrrolidinone,diol-terminated polyacrylamides, diol-terminated polyethylene oxides,and diol-terminated polyethylene oxide (PEO)/polypropylene oxide (PPO)block copolymers.

It would be desirable to provide improved surface modified biomedicaldevices having an optically clear, hydrophilic coating on the surfacethereof that renders the device more biocompatible. In addition, itwould also be desirable to form a coating on a contact lens havingimproved wettability and lubriciousness while also inhibiting attachmentof microorganisms to the surface of the lens, thus making the lens morecomfortable to wear for a longer period of time. In this manner, thebiocompatibilized lens can be capable of continuous wear overnight,preferably for a week or more without adverse effects to the cornea.

SUMMARY OF THE INVENTION

In accordance with one embodiment of the present invention, a brushcopolymer is provided comprising (a) monomeric units derived from anethylenically unsaturated-containing monomer containing one or moreboronic acid moieties; and (b) monomeric units derived from anethylenically unsaturated-containing macromonomer having hydrophilicunits and boronic acid units.

In accordance with a second embodiment of the present invention, a brushcopolymer is provided comprising monomeric units derived from anethylenically unsaturated-containing monomer containing one or moreboronic acid moieties in the backbone of the polymer; and bristles ofmonomeric units derived from an ethylenically unsaturated-containingmacromonomer having hydrophilic units and boronic acid units.

In accordance with a third embodiment of the present invention, abiomedical device having a coating on at least a portion of a surfacethereof is provided, the coating comprising a brush copolymer comprising(a) monomeric units derived from an ethylenically unsaturated-containingmonomer containing one or more boronic acid moieties; and (b) monomericunits derived from an ethylenically unsaturated-containing macromonomerhaving hydrophilic units and boronic acid units.

In accordance with a fourth embodiment of the present invention, amethod for making a biomedical device is provided, the method comprisingexposing a biomedical device having a plurality of biomedical devicesurface functional groups to one or more brush copolymers comprising (a)monomeric units derived from an ethylenically unsaturated-containingmonomer containing one or more boronic acid moieties; and (b) monomericunits derived from an ethylenically unsaturated-containing macromonomerhaving hydrophilic units and boronic acid units, thus forming abiocompatible surface on the biomedical device.

In accordance with a fifth embodiment of the present invention, apackaging system for the storage of an ophthalmic device is providedcomprising a sealed container containing one or more unused ophthalmicdevices immersed in an aqueous packaging solution comprising one or morebrush copolymers comprising (a) monomeric units derived from anethylenically unsaturated-containing monomer containing one or moreboronic acid moieties; and (b) monomeric units derived from anethylenically unsaturated-containing macromonomer having hydrophilicunits and boronic acid units, wherein the solution has an osmolality ofat least about 200 mOsm/kg, a pH of about 6 to about 9 and is heatsterilized.

The brush copolymers of the present invention contain boronic acidmoieties in the backbone of the brush copolymer which attach tobiomedical device surface functional groups on the surface of abiomedical device while the bristles of monomeric units derived from anethylenically unsaturated-containing macromonomer having hydrophilicunits and boronic acid units provide a hydrophilic or lubricious (orboth) surface while also being capable of complexing with mucin via theboronic acid moieties of the macromonomer. Accordingly, the brushcopolymers of the present invention advantageously provide improvedsurface treated biomedical devices exhibiting a higher level ofperformance quality and/or comfort to the users due to their hydrophilicor lubricious (or both) surfaces. Hydrophilic and/or lubricious surfacesof the biomedical devices herein such as contact lenses substantiallyprevent or limit the adsorption of tear lipids and proteins on, andtheir eventual absorption into, the lenses, thus preserving the clarityof the contact lenses. This, in turn, preserves their performancequality thereby providing a higher level of comfort to the wearer.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is directed to brush copolymers useful in treatingthe surface of a biomedical device intended for direct contact with bodytissue or fluid. In general, “polymer brushes,” contain polymer chains,one end of which is directly or indirectly tethered to a surface andanother end of which is free to extend from the surface, somewhatanalogous to the bristles of a brush. The brush copolymers of thepresent invention have at least one or more types of boronic acidpolymer chains, which attach to biomedical device surface functionalgroups on the surface of a biomedical device, and one or more types ofmacromonomer polymer chains having hydrophilic units and boronic acidunits, which do not attach to biomedical device surface functionalgroups on the surface of a biomedical device but may complex with mucin,especially epithelial mucin, by way of the boronic acid moieties. In oneembodiment, the brush polymers of the present invention contain at least(a) monomeric units derived from an ethylenically unsaturated-containingmonomer containing one or more boronic acid moieties and; and (b)monomeric units derived from an ethylenically unsaturated-containingmacromonomer having hydrophilic units and boronic acid units.

Representative examples of suitable ethylenically unsaturated monomerscontaining one or more boronic acid moieties include ethylenicallyunsaturated-containing alkyl boronic acids; ethylenicallyunsaturated-containing cycloalkyl boronic acids; ethylenicallyunsaturated-containing aryl boronic acids and the like and mixturesthereof. Preferred ethylenically unsaturated monomers having one or moreboronic acid moieties include 4-vinylphenylboronic acid,3-methacrylamidophenylboronic acid, 3-acrylamidophenylboronic acid andmixtures thereof.

Representative examples of alkyl groups for use herein include, by wayof example, a straight or branched hydrocarbon chain radical containingcarbon and hydrogen atoms of from 1 to about 18 carbon atoms with orwithout unsaturation, to the rest of the molecule, e.g., methyl, ethyl,n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, etc., and thelike.

Representative examples of cycloalkyl groups for use herein include, byway of example, a substituted or unsubstituted non-aromatic mono ormulticyclic ring system of about 3 to about 24 carbon atoms such as, forexample, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,perhydronapththyl, adamantyl and norbornyl groups bridged cyclic groupor sprirobicyclic groups, e.g., sprio-(4,4)-non-2-yl and the like,optionally containing one or more heteroatoms, e.g., O and N, and thelike.

Representative examples of aryl groups for use herein include, by way ofexample, a substituted or unsubstituted monoaromatic or polyaromaticradical containing from about 5 to about 30 carbon atoms such as, forexample, phenyl, naphthyl, tetrahydronapthyl, indenyl, biphenyl and thelike, optionally containing one or more heteroatoms, e.g., O and N, andthe like.

Representative examples of the ethylenically unsaturated moiety of theethylenically unsaturated monomer include, by way of example,(meth)acrylate-containing radicals, (meth)acrylamido-containingradicals, vinylcarbonate-containing radicals, vinylcarbamate-containingradicals, styrene-containing radicals, itaconate-containing radicals,vinyl-containing radicals, vinyloxy-containing radicals,fumarate-containing radicals, maleimide-containing radicals,vinylsulfonyl radicals and the like. As used herein, the term “(meth)”denotes an optional methyl substituent. Thus, for example, terms such as“(meth)acrylate” denotes either methacrylate or acrylate, and“(meth)acrylamide” denotes either methacrylamide or acrylamide.

In one embodiment, an ethylenically unsaturated moiety of theethylenically unsaturated boronic acid-containing monomer is representedby the general formula:

wherein R is hydrogen or a alkyl group having 1 to 6 carbon atoms suchas methyl; each R is independently hydrogen, an alkyl radical having 1to 6 carbon atoms, or a —CO—Y—R′″ radical wherein Y is —O—, —S— or —NH—and R′″ an alkyl radical having 1 to about 10 carbon atoms; R″ is alinking group (e.g., a divalent alkenyl radical having 1 to about 12carbon atoms); B denotes —O— or —NH—; Z denotes —CO—, —OCO— or —COO—; Ardenotes an aromatic radical having 6 to about 30 carbon atoms; w is 0 to6; a is 0 or 1; b is 0 or 1; and c is 0 or 1. The ethylenicallyunsaturated-containing moiety can be attached to the boronicacid-containing monomers as pendent groups, terminal groups or both.

The brush copolymers further include monomeric units derived from anethylenically unsaturated-containing macromonomer having hydrophilicunits and boronic acid units. As used herein, the term “macromonomer”denotes high molecular weight polymers that can be prepared by, forexample, free radical polymerization. In general, the macromonomers havea number average molecular weight of about 500 to about 200,000 andpreferably from about 500 to about 20,000. The hydrophilic units arederived from a hydrophilic monomer such as, for example, acrylamidessuch as N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, and thelike; acetamides such as N-vinyl-N-methyl acetamide, N-vinyl acetamideand the like; formamides such as N-vinyl-N-methyl formamide, N-vinylformamide, and the like; cyclic lactams such as N-vinyl-2-pyrrolidoneand the like; (meth)acrylated alcohols such as 2-hydroxyethylmethacrylate, 2-hydroxyethyl acrylate and the like; (meth)acrylatedpoly(ethyleneglycol)s and the like and mixtures thereof. The boronicacid units can be derived from any of the boronic acid monomersdiscussed above.

The ethylenically unsaturated-containing moiety can be any of theethylenically unsaturated-containing moieties discussed hereinabove. Asone skilled in the art will readily appreciate, the ethylenicallyunsaturated-containing moiety can be attached to the hydrophilic monomeras a pendent group, terminal group or both.

In one embodiment, the ethylenically unsaturated-containingmacromonomers having hydrophilic units and boronic acid units can beobtained by first (1) mixing the hydrophilic monomer and boronic acidmonomer with a suitable chain transfer agent; (2) adding apolymerization initiator; (3) and subjecting the monomer/initiatormixture to a source of heat. Suitable chain transfer agents include, butare not limited to, thiol glycolic acid, hydroxyethylmercaptan,mercaptoethanol; and the like. Typical initiators includefree-radical-generating polymerization initiators of the typeillustrated by acetyl peroxide, lauroyl peroxide, decanoyl peroxide,coprylyl peroxide, benzoyl peroxide, tertiary butyl peroxypivalate,sodium percarbonate, tertiary butyl peroctoate, andazobis-isobutyronitrile (AIBN). The level of initiator employed willvary within the range of 0.01 to 2 weight percent of the mixture ofmonomers. Usually, a mixture of the above-mentioned monomers is warmedwith addition of a free-radical former.

The reaction can be carried out at a temperature of between about 50° C.to about 70° C. for about 12 to about 72 hours. The reaction can becarried out in the presence of a suitable solvent. Suitable solvents arein principle all solvents which dissolve the monomer used, for example,carboxamides such as dimethylformamide; dipolar aprotic solvents such asdimethyl sulfoxide; ketones such as acetone or cyclohexanone;hydrocarbons such as toluene and the like.

Next, the ethylenically unsaturated-containing moiety is introduced byusing an excess of, for example, methacrylic anhydride, and in thepresence of an amine scavenger such as 4-dimethylaminopyridine. Thereaction can be carried out at room temperature.

The ethylenically unsaturated-containing macromonomers havinghydrophilic units and boronic acid units may contain about 90 to about98 mole percent of hydrophilic units, and preferably about 2 to about 10mole percent, and about 1 to about 20 mole percent of the boronic acidunits, and preferably about 2 to about 10 mole percent.

The brush copolymers can further include a monomeric unit containing atertiary-amine terminal moiety in the backbone of the polymer. Suitablemonomers copolymerizable with the boronic acid monomer and hydrophilicmacromonomer are ethylenically unsaturated monomers containing atertiary-amine moiety. Representative examples include, but are notlimited to, 2-(N,N-dimethyl)ethylamino(meth)acrylate,N-[2-(dimethylamino)ethyl](meth)acrylamide, N-[(3-dimethylamino)propyl](meth)acrylate, N-[3-dimethylamino)propyl](meth)acrylamide,vinylbenzyl-N,N-dimethylamine and the like and mixtures thereof.

The brush copolymers of the present invention may further include amonomeric unit containing a hydrophilic moiety in the backbone of thepolymer. Representative examples include, but are not limited to,N,N-dimethylacrylamide, N,N-dimethylmethacrylamide and the like;acetamides such as N-vinyl-N-methyl acetamide and N-vinyl acetamide andthe like; formamides such as N-vinyl-N-methyl formamide and N-vinylformamide, and the like; 2cyclic lactams such as N-vinyl-2-pyrrolidoneand the like; (meth)acrylated alcohols such as 2-hydroxyethylmethacrylate, 2-hydroxyethyl acrylate and the like; (meth)acrylatedpoly(ethyleneglycol)s and the like and mixtures thereof. The hydrophilicmonomeric unit in the polymer, when used, ensures that the copolymer iswater-soluble, thus avoiding the need to dissolve the copolymer inorganic solvent when applying the polymer to the lens surface.

One class of brush copolymers are copolymers containing (a) monomericunits derived from an ethylenically unsaturated-containing monomercontaining one or more boronic acid moieties, (b) monomeric unitsderived from an ethylenically unsaturated-containing macromonomer havinghydrophilic units and boronic acid units, (c) monomeric units derivedfrom the ethylenically unsaturated monomer containing a tertiary-aminemoiety, and (d) monomeric units derived from an ethylenicallyunsaturated hydrophilic monomer in an amount sufficient to render thecopolymer water soluble. This class of copolymers may contain about 1 toabout 20 mole percent of the boronic acid-containing monomeric units,and preferably about 2 to about 10 mole percent; about 1 to about 20mole percent of monomeric units derived from an ethylenicallyunsaturated-containing macromonomer having hydrophilic units and boronicacid units, and preferably about 2 to about 10 mole percent, 1 to about20 mole percent of the tertiary-amine-containing monomeric units, andpreferably about 2 to about 10 mole percent; and 40 to about 90 molepercent of the hydrophilic monomeric units, and preferably about 50 toabout 80 mole percent.

The brush copolymers of the present invention can be obtained by apolymerization reaction customary to the person skilled in the art.Typically, the polymers or chains are formed by subjecting amonomers/photoinitiator mixture to a source of ultraviolet or actinicradiation and/or elevated temperature and curing the mixture. Typicalpolymerization initiators include free-radical-generating polymerizationinitiators such as acetyl peroxide, lauroyl peroxide, decanoyl peroxide,caprylyl peroxide, benzoyl peroxide, tertiary butyl peroxypivalate,sodium percarbonate, tertiary butyl peroctoate, andazobis-isobutyronitrile (AIBN). Typical ultraviolet free-radicalinitiators such as diethoxyacetophenone can also be used. The curingprocess will of course depend upon the initiator used and the physicalcharacteristics of the monomer or monomer mixture such as viscosity. Inany event, the level of initiator employed will vary within the range ofabout 0.001 to about 2 weight percent of the mixture of monomers.

Polymerization to form the resulting brush polymers can be carried outin the presence or absence of a solvent. Suitable solvents are inprinciple a solvent is capable of dissolving all of the monomers presentin the monomer mixture. In a preferred embodiment, a suitable solvent isa polar solvent such as, for example, water; alcohols such as loweralkanols, for example, methanol and ethanol; and the like.

In another embodiment of the present invention, biomedical devices areprovided which comprise the brush copolymers of the present invention attheir surfaces. The brush copolymer may be provided over the entiresurface of the biomedical device or over only a portion of thebiomedical device surface. As used herein, the term “biomedical device”shall be understood to mean any article that is designed to be usedwhile either in or on mammalian tissues or fluid, and preferably in oron human tissue or fluids. Representative examples of biomedical devicesinclude, but are not limited to, artificial ureters, diaphragms,intrauterine devices, heart valves, catheters, denture liners,prosthetic devices, ophthalmic lens applications, where the lens isintended for direct placement in or on the eye, such as, for example,intraocular devices and contact lenses. The preferred biomedical devicesare ophthalmic devices, particularly contact lenses, and mostparticularly contact lenses made from silicone hydrogels.

As used herein, the term “ophthalmic device” refers to devices thatreside in or on the eye. These devices can provide optical correction,wound care, drug delivery, diagnostic functionality or cosmeticenhancement or effect or a combination of these properties. Usefulophthalmic devices include, but are not limited to, ophthalmic lensessuch as soft contact lenses, e.g., a soft, hydrogel lens; soft,non-hydrogel lens and the like, hard contact lenses, e.g., a hard, gaspermeable lens material and the like, intraocular lenses, overlaylenses, ocular inserts, optical inserts and the like. As is understoodby one skilled in the art, a lens is considered to be “soft” if it canbe folded back upon itself without breaking.

The biomedical devices to be surface modified according to the presentinvention can be any material known in the art capable of forming abiomedical device as described above. In one embodiment, a biomedicaldevice includes devices formed from material not hydrophilic per se.Such devices are formed from materials known in the art and include, byway of example, polysiloxanes, perfluoropolyethers, fluorinatedpoly(meth)acrylates or equivalent fluorinated polymers derived, e.g.,from other polymerizable carboxylic acids, polyalkyl (meth)acrylates orequivalent alkylester polymers derived from other polymerizablecarboxylic acids, or fluorinated polyolefins, such as fluorinatedethylene propylene polymers, or tetrafluoroethylene, preferably incombination with a dioxol, e.g., perfluoro-2,2-dimethyl-1,3-dioxol.Representative examples of suitable bulk materials include, but are notlimited to, Lotrafilcon A, Neofocon, Pasifocon, Telefocon, Silafocon,Fluorsilfocon, Paflufocon, Silafocon, Elastofilcon, Fluorofocon orTeflon AF materials, such as Teflon AF 1600 or Teflon AF 2400 which arecopolymers of about 63 to about 73 mol % ofperfluoro-2,2-dimethyl-1,3-dioxol and about 37 to about 27 mol % oftetrafluoroethylene, or of about 80 to about 90 mol % ofperfluoro-2,2-dimethyl-1,3-dioxol and about 20 to about 10 mol % oftetrafluoroethylene.

In another embodiment, a biomedical device includes devices formed frommaterial hydrophilic per se, since reactive groups, e.g., carboxy,carbamoyl, sulfate, sulfonate, phosphate, amine, ammonium or hydroxygroups, are inherently present in the material and therefore also at thesurface of a biomedical device manufactured therefrom. Such devices areformed from materials known in the art and include, by way of example,polyhydroxyethyl acrylate, polyhydroxyethyl methacrylate, polyvinylpyrrolidone (PVP), polyacrylic acid, polymethacrylic acid,polyacrylamide, polydimethylacrylamide (DMA), polyvinyl alcohol and thelike and copolymers thereof, e.g., from two or more monomers selectedfrom hydroxyethyl acrylate, hydroxyethyl methacrylate, N-vinylpyrrolidone, acrylic acid, methacrylic acid, acrylamide, dimethylacrylamide, vinyl alcohol and the like. Representative examples ofsuitable bulk materials include, but are not limited to, Polymacon,Tefilcon, Methafilcon, Deltafilcon, Bufilcon, Phemfilcon, Ocufilcon,Focofilcon, Etafilcon, Hefilcon, Vifilcon, Tetrafilcon, Perfilcon,Droxifilcon, Dimefilcon, Isofilcon, Mafilcon, Nelfilcon, Atlafilcon andthe like. Examples of other suitable bulk materials include BalafilconA, Hilafilcon A, Alphafilcon A, Bilafilcon B and the like.

In another embodiment, biomedical devices to be surface modifiedaccording to the present invention include devices which are formed frommaterial which are amphiphilic segmented copolymers containing at leastone hydrophobic segment and at least one hydrophilic segment which arelinked through a bond or a bridge member.

It is particularly useful to employ biocompatible materials hereinincluding both soft and rigid materials commonly used for ophthalmiclenses, including contact lenses. In general, non-hydrogel materials arehydrophobic polymeric materials that do not contain water in theirequilibrium state. Typical non-hydrogel materials comprise siliconeacrylics, such as those formed bulky silicone monomer (e.g.,tris(trimethylsiloxy)silylpropyl methacrylate, commonly known as “TRIS”monomer), methacrylate end-capped poly(dimethylsiloxane) prepolymer, orsilicones having fluoroalkyl side groups (polysiloxanes are alsocommonly known as silicone polymers).

On the other hand, hydrogel materials comprise hydrated, cross-linkedpolymeric systems containing water in an equilibrium state. Hydrogelmaterials contain about 5 weight percent water or more (up to, forexample, about 80 weight percent). The preferred hydrogel materials,include silicone hydrogel materials. In one preferred embodiment,materials include vinyl functionalized polydimethylsiloxanescopolymerized with hydrophilic monomers as well as fluorinatedmethacrylates and methacrylate functionalized fluorinated polyethyleneoxides copolymerized with hydrophilic monomers. Representative examplesof suitable materials for use herein include those disclosed in U.S.Pat. Nos. 5,310,779; 5,387,662; 5,449,729; 5,512,205; 5,610,252;5,616,757; 5,708,094; 5,710,302; 5,714,557 and 5,908,906, the contentsof which are incorporated by reference herein.

In one embodiment, hydrogel materials for biomedical devices, such ascontact lenses, can contain a hydrophilic monomer such as one or moreunsaturated carboxylic acids, vinyl lactams, amides, polymerizableamines, vinyl carbonates, vinyl carbamates, oxazolone monomers,copolymers thereof and the like and mixtures thereof. Useful amidesinclude acrylamides such as N,N-dimethylacrylamide andN,N-dimethylmethacrylamide. Useful vinyl lactams include cyclic lactamssuch as N-vinyl-2-pyrrolidone. Examples of other hydrophilic monomersinclude hydrophilic prepolymers such as poly(alkene glycols)functionalized with polymerizable groups. Examples of usefulfunctionalized poly(alkene glycols) include poly(diethylene glycols) ofvarying chain length containing monomethacrylate or dimethacrylate endcaps. In a preferred embodiment, the poly(alkene glycol) polymercontains at least two alkene glycol monomeric units. Still furtherexamples are the hydrophilic vinyl carbonate or vinyl carbamate monomersdisclosed in U.S. Pat. No. 5,070,215, and the hydrophilic oxazolonemonomers disclosed in U.S. Pat. No. 4,910,277. Other suitablehydrophilic monomers will be apparent to one skilled in the art. Inanother embodiment, a hydrogel material can contain asiloxane-containing monomer and at least one of the aforementionedhydrophilic monomers and/or prepolymers.

Non-limited examples of hydrophobic monomers are C₁-C₂₀ alkyl and C₃-C₂₀cycloalkyl (meth)acrylates, substituted and unsubstituted aryl(meth)acrylates (wherein the aryl group comprises 6 to 36 carbon atoms),(meth)acrylonitrile, styrene, lower alkyl styrene, lower alky vinylethers, and C₂-C₁₀ perfluoroalkyl (meth)acrylates and correspondinglypartially fluorinate (meth)acrylates.

A wide variety of materials can be used herein, and silicone hydrogelcontact lens materials are particularly preferred. Silicone hydrogelsgenerally have a water content greater than about 5 weight percent andmore commonly between about 10 to about 80 weight percent. Suchmaterials are usually prepared by polymerizing a mixture containing atleast one silicone-containing monomer and at least one hydrophilicmonomer. Typically, either the silicone-containing monomer or thehydrophilic monomer functions as a crosslinking agent (a crosslinkerbeing defined as a monomer having multiple polymerizablefunctionalities) or a separate crosslinker may be employed. Applicablesilicone-containing monomers for use in the formation of siliconehydrogels are well known in the art and numerous examples are providedin U.S. Pat. Nos. 4,136,250; 4,153,641; 4,740,533; 5,034,461; 5,070,215;5,260,000; 5,310,779; and 5,358,995.

Representative examples of applicable silicon-containing monomersinclude bulky polysiloxanylalkyl(meth)acrylic monomers. An example of abulky polysiloxanylalkyl(meth)acrylic monomer is represented by thestructure of Formula I:

wherein X denotes —O— or —NR— wherein R denotes hydrogen or a C₁-C₄alkyl; each R¹ independently denotes hydrogen or methyl; each R²independently denotes a lower alkyl radical, phenyl radical or a grouprepresented by

wherein each R^(2′) independently denotes a lower alkyl or phenylradical; and h is 1 to 10.

Representative examples of other applicable silicon-containing monomersincludes, but are not limited to, bulky polysiloxanylalkyl carbamatemonomers as generally depicted in Formula Ia:

wherein X denotes —NR—; wherein R denotes hydrogen or a C₁-C₄ alkyl; R¹denotes hydrogen or methyl; each R² independently denotes a lower alkylradical, phenyl radical or a group represented by

wherein each R² independently denotes a lower alkyl or phenyl radical;and h is 1 to 10, and the like.

Examples of bulky monomers are3-methacryloyloxypropyltris(trimethyl-siloxy)silane ortris(trimethylsiloxy)silylpropyl methacrylate, sometimes referred to asTRIS and tris(trimethylsiloxy)silylpropyl vinyl carbamate, sometimesreferred to as TRIS-VC and the like and mixtures thereof.

Such bulky monomers may be copolymerized with a silicone macromonomer,which is a poly(organosiloxane) capped with an unsaturated group at twoor more ends of the molecule. U.S. Pat. No. 4,153,641 discloses, forexample, various unsaturated groups such as acryloxy or methacryloxygroups.

Another class of representative silicone-containing monomers includes,but is not limited to, silicone-containing vinyl carbonate or vinylcarbamate monomers such as, for example,1,3-bis[4-vinyloxylcarbonyloxy)but-1-yl]tetramethyl-disiloxane;3-(trimethylsilyl)propyl vinyl carbonate;3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl vinylcarbonate; trimethylsilylmethyl vinyl carbonate and the like andmixtures thereof.

Another class of silicon-containing monomers includespolyurethane-polysiloxane macromonomers (also sometimes referred to asprepolymers), which may have hard-soft-hard blocks like traditionalurethane elastomers. They may be end-capped with a hydrophilic monomersuch as HEMA. Examples of such silicone urethanes are disclosed in avariety or publications, including Lai, Yu-Chin, “The Role of BulkyPolysiloxanylalkyl Methacryates in Polyurethane-Polysiloxane Hydrogels,”Journal of Applied Polymer Science, Vol. 60, 1193-1199 (1996). PCTPublished Application No. WO 96/31792 discloses examples of suchmonomers, which disclosure is hereby incorporated by reference in itsentirety. Further examples of silicone urethane monomers are representedby Formulae II and III:

E(*D*A*D*G)_(a)*D*A*D*E′; or  (II)

E(*D*G*D*A)_(a)*D*A*D*E′; or  (III)

wherein:

D independently denotes an alkyl diradical, an alkyl cycloalkyldiradical, a cycloalkyl diradical, an aryl diradical or an alkylaryldiradical having 6 to about 30 carbon atoms;

G independently denotes an alkyl diradical, a cycloalkyl diradical, analkyl cycloalkyl diradical, an aryl diradical or an alkylaryl diradicalhaving 1 to about 40 carbon atoms and which may contain ether, thio oramine linkages in the main chain;

* denotes a urethane or ureido linkage;

a is at least 1;

A independently denotes a divalent polymeric radical of Formula IV:

wherein each R^(s) independently denotes an alkyl or fluoro-substitutedalkyl group having 1 to about 10 carbon atoms which may contain etherlinkages between the carbon atoms; m′ is at least 1; and p is a numberthat provides a moiety weight of about 400 to about 10,000;

each of E and E′ independently denotes a polymerizable unsaturatedorganic radical represented by Formula V:

wherein: R³ is hydrogen or methyl;R⁴ is hydrogen, an alkyl radical having 1 to 6 carbon atoms, or a—CO—Y—R⁶ radical wherein Y is —O—, —S— or —NH—;R⁵ is a divalent alkylene radical having 1 to about 10 carbon atoms;R⁶ is a alkyl radical having 1 to about 12 carbon atoms;X denotes —CO— or —OCO—;Z denotes —O— or —NH—;Ar denotes an aromatic radical having about 6 to about 30 carbon atoms;w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.

A preferred silicone-containing urethane monomer is represented byFormula VI:

wherein m is at least 1 and is preferably 3 or 4, a is at least 1 andpreferably is 1, p is a number which provides a moiety weight of about400 to about 10,000 and is preferably at least about 30, R⁷ is adiradical of a diisocyanate after removal of the isocyanate group, suchas the diradical of isophorone diisocyanate, and each E″ is a grouprepresented by:

In another embodiment of the present invention, a silicone hydrogelmaterial comprises (in bulk, that is, in the monomer mixture that iscopolymerized) about 5 to about 50 percent, and preferably about 10 toabout 25, by weight of one or more silicone macromonomers, about 5 toabout 75 percent, and preferably about 30 to about 60 percent, by weightof one or more polysiloxanylalkyl (meth)acrylic monomers, and about 10to about 50 percent, and preferably about 20 to about 40 percent, byweight of a hydrophilic monomer. In general, the silicone macromonomeris a poly(organosiloxane) capped with an unsaturated group at two ormore ends of the molecule. In addition to the end groups in the abovestructural formulas, U.S. Pat. No. 4,153,641 discloses additionalunsaturated groups, including acryloxy or methacryloxy.Fumarate-containing materials such as those disclosed in U.S. Pat. Nos.5,310,779; 5,449,729 and 5,512,205 are also useful substrates inaccordance with the invention. The silane macromonomer may be asilicon-containing vinyl carbonate or vinyl carbamate or apolyurethane-polysiloxane having one or more hard-soft-hard blocks andend-capped with a hydrophilic monomer.

Another class of representative silicone-containing monomers includesfluorinated monomers. Such monomers have been used in the formation offluorosilicone hydrogels to reduce the accumulation of deposits oncontact lenses made therefrom, as disclosed in, for example, U.S. Pat.Nos. 4,954,587; 5,010,141 and 5,079,319. Also, the use ofsilicone-containing monomers having certain fluorinated side groups,i.e., —(CF₂)—H, have been found to improve compatibility between thehydrophilic and silicone-containing monomeric units. See, e.g., U.S.Pat. Nos. 5,321,108 and 5,387,662.

The above silicone materials are merely exemplary, and other materialsfor use as substrates that can benefit by being coated with thehydrophilic coating composition according to the present invention andhave been disclosed in various publications and are being continuouslydeveloped for use in contact lenses and other medical devices can alsobe used. For example, a biomedical device can be formed from at least acationic monomer such as cationic silicone-containing monomer orcationic fluorinated silicone-containing monomers.

Contact lenses for application of the present invention can bemanufactured employing various conventional techniques, to yield ashaped article having the desired posterior and anterior lens surfaces.Spincasting methods are disclosed in U.S. Pat. Nos. 3,408,429 and3,660,545; and static casting methods are disclosed in U.S. Pat. Nos.4,113,224, 4,197,266 and 5,271,876. Curing of the monomeric mixture maybe followed by a machining operation in order to provide a contact lenshaving a desired final configuration. As an example, U.S. Pat. No.4,555,732 discloses a process in which an excess of a monomeric mixtureis cured by spincasting in a mold to form a shaped article having ananterior lens surface and a relatively large thickness. The posteriorsurface of the cured spincast article is subsequently lathe cut toprovide a contact lens having the desired thickness and posterior lenssurface. Further machining operations may follow the lathe cutting ofthe lens surface, for example, edge-finishing operations.

Typically, an organic diluent is included in the initial monomericmixture in order to minimize phase separation of polymerized productsproduced by polymerization of the monomeric mixture and to lower theglass transition temperature of the reacting polymeric mixture, whichallows for a more efficient curing process and ultimately results in amore uniformly polymerized product. Sufficient uniformity of the initialmonomeric mixture and the polymerized product is of particularimportance for silicone hydrogels, primarily due to the inclusion ofsilicone-containing monomers which may tend to separate from thehydrophilic comonomer.

Suitable organic diluents include, for example, monohydric alcohols suchas C₆-C₁₀ straight-chained aliphatic monohydric alcohols, e.g.,n-hexanol and n-nonanol; diols such as ethylene glycol; polyols such asglycerin; ethers such as diethylene glycol monoethyl ether; ketones suchas methyl ethyl ketone; esters such as methyl enanthate; andhydrocarbons such as toluene. Preferably, the organic diluent issufficiently volatile to facilitate its removal from a cured article byevaporation at or near ambient pressure.

Generally, the diluent may be included at about 5 to about 60 percent byweight of the monomeric mixture, with about 10 to about 50 percent byweight being especially preferred. If necessary, the cured lens may besubjected to solvent removal, which can be accomplished by evaporationat or near ambient pressure or under vacuum. An elevated temperature canbe employed to shorten the time necessary to evaporate the diluent.

Following removal of the organic diluent, the lens can then be subjectedto mold release and optional machining operations. The machining stepincludes, for example, buffing or polishing a lens edge and/or surface.Generally, such machining processes may be performed before or after thearticle is released from a mold part. As an example, the lens may be dryreleased from the mold by employing vacuum tweezers to lift the lensfrom the mold.

As one skilled in the art will readily appreciate, biomedical devicesurface functional groups of the biomedical device according to thepresent invention may be inherently present at the surface of thedevice. However, if the biomedical device contains too few or nofunctional groups, the surface of the device can be modified by knowntechniques, for example, plasma chemical methods (see, for example, WO94/06485), or conventional functionalization with groups such as —OH, or—CO₂H. Suitable biomedical device surface functional groups of thebiomedical device include a wide variety of groups well known to theskilled artisan. Representative examples of such functional groupsinclude, but are not limited to, hydroxy groups, c is 1,2-diols, c is1,3-diols, a hydroxyl groups (e.g., sialic acid, salicylic acid),carboxylic acids, di-carboxylic acids, catechols, silanols, silicatesand the like.

In a preferred embodiment, the foregoing biomedical devices aresubjected to an oxidative surface treatment such as corona discharge orplasma oxidation followed by treatment with the brush copolymers of thepresent invention. The biomedical devices such as silicone hydrogelformulations containing hydrophilic polymers, such aspoly(N,N-dimethylacrylamide) or poly(N-vinylpyrrolidinone), aresubjected to a surface treatment and then treated with an aqueoussolution containing the brush copolymer of the present invention torender a lubricious, stable, highly wettable brush copolymer basedsurface coating. The complexation treatment is advantageously performedunder autoclave conditions (sterilization conditions).

The standard process such as a plasma process (also referred to as“electrical glow discharge processes”) provides a thin, durable surfaceupon the biomedical device preliminary to the attachment of the brushcopolymers. Examples of such plasma processes are provided in U.S. Pat.Nos. 4,143,949; 4,312,575; and 5,464,667.

Although plasma processes are generally well known in the art, a briefoverview is provided below. Plasma surface treatments involve passing anelectrical discharge through a gas at low pressure. The electricaldischarge may be at radio frequency (typically 13.56 MHz), althoughmicrowave and other frequencies can be used. Electrical dischargesproduce ultraviolet (UV) radiation, in addition to being absorbed byatoms and molecules in their gas state, resulting in energetic electronsand ions, atoms (ground and excited states), molecules, and radicals.Thus, a plasma is a complex mixture of atoms and molecules in bothground and excited states, which reach a steady state after thedischarge is begun. The circulating electrical field causes theseexcited atoms and molecules to collide with one another as well as thewalls of the chamber and the surface of the material being treated.

The deposition of a coating from a plasma onto the surface of a materialhas been shown to be possible from high-energy plasmas without theassistance of sputtering (sputter-assisted deposition). Monomers can bedeposited from the gas phase and polymerized in a low pressureatmosphere (about 0.005 to about 5 torr, and preferably about 0.001 toabout 1 torr) onto a substrate utilizing continuous or pulsed plasmas,suitably as high as about 1000 watts. A modulated plasma, for example,may be applied about 100 milliseconds on then off. In addition, liquidnitrogen cooling has been utilized to condense vapors out of the gasphase onto a substrate and subsequently use the plasma to chemicallyreact these materials with the substrate. However, plasmas do notrequire the use of external cooling or heating to cause the deposition.Low or high wattage (e.g., about 5 to about 1000, and preferably about20 to about 500 watts) plasmas can coat even the most chemical-resistantsubstrates, including silicones.

After initiation by a low energy discharge, collisions between energeticfree electrons present in the plasma cause the formation of ions,excited molecules, and free-radicals. Such species, once formed, canreact with themselves in the gas phase as well as with furtherground-state molecules. The plasma treatment may be understood as anenergy dependent process involving energetic gas molecules. For chemicalreactions to take place at the surface of the lens, one needs therequired species (element or molecule) in terms of charge state andparticle energy. Radio frequency plasmas generally produce adistribution of energetic species. Typically, the “particle energy”refers to the average of the so-called Boltzman-style distribution ofenergy for the energetic species. In a low-density plasma, the electronenergy distribution can be related by the ratio of the electric fieldstrength sustaining the plasma to the discharge pressure (E/p). Theplasma power density P is a function of the wattage, pressure, flowrates of gases, etc., as will be appreciated by the skilled artisan.Background information on plasma technology, hereby incorporated byreference, includes the following: A. T. Bell, Proc. Intl. Conf. Phenom.Ioniz. Gases, “Chemical Reaction in Nonequilibrium Plasmas”, 19-33(1977); J. M. Tibbitt, R. Jensen, A. T. Bell, M. Shen, Macromolecules,“A Model for the Kinetics of Plasma Polymerization”, 3, 648-653 (1977);J. M. Tibbitt, M. Shen, A. T. Bell, J. Macromol. Sci.-Chem., “StructuralCharacterization of Plasma-Polymerized Hydrocarbons”, A10, 1623-1648(1976); C. P. Ho, H. Yasuda, J. Biomed, Mater. Res., “Ultrathin coatingof plasma polymer of methane applied on the surface of silicone contactlenses”, 22, 919-937 (1988); H. Kobayashi, A. T. Bell, M. Shen,Macromolecules, “Plasma Polymerization of Saturated and UnsaturatedHydrocarbons”, 3, 277-283 (1974); R. Y. Chen, U.S. Pat. No. 4,143,949,Mar. 13, 1979, “Process for Putting a Hydrophilic Coating on aHydrophobic Contact lens”; and H. Yasuda, H. C. Marsh, M. O. Bumgarner,N. Morosoff, J. of Appl. Poly. Sci., “Polymerization of OrganicCompounds in an Electroless Glow Discharge. VI. Acetylene with UnusualCo-monomers”, 19, 2845-2858 (1975).

Based on this previous work in the field of plasma technology, theeffects of changing pressure and discharge power on the rate of plasmamodification can be understood. The rate generally decreases as thepressure is increased. Thus, as pressure increases the value of E/p, theratio of the electric field strength sustaining the plasma to the gaspressure decreases and causes a decrease in the average electron energy.The decrease in electron energy in turn causes a reduction in the ratecoefficient of all electron-molecule collision processes. A furtherconsequence of an increase in pressure is a decrease in electrondensity. Providing that the pressure is held constant, there should be alinear relationship between electron density and power.

In practice, contact lenses are surface-treated by placing them, intheir unhydrated state, within an electric glow discharge reactionvessel (e.g., a vacuum chamber). Such reaction vessels are commerciallyavailable. The lenses may be supported within the vessel on an aluminumtray (which acts as an electrode) or with other support devices designedto adjust the position of the lenses. The use of a specialized supportdevices which permit the surface treatment of both sides of a lens areknown in the art and may be used herein.

As mentioned above, the surface of the lens, for example, a siliconehydrogel continuous-wear lens is initially treated, e.g., oxidized, bythe use of a plasma to render the subsequent brush copolymer surfacedeposition more adherent to the lens. Such a plasma treatment of thelens may be accomplished in an atmosphere composed of a suitable media,e.g., an oxidizing media such as oxygen, air, water, peroxide, O₂(oxygen gas), etc., or appropriate combinations thereof, typically at anelectric discharge frequency of about 13.56 Mhz, preferably betweenabout 20 to about 500 watts at a pressure of about 0.1 to about 1.0torr, preferably for about 10 seconds to about 10 minutes or more, morepreferably about 1 to about 10 minutes. It is preferred that arelatively “strong” plasma is utilized in this step, for example,ambient air drawn through a five percent (5%) hydrogen peroxidesolution. Those skilled in the art will know other methods of improvingor promoting adhesion for bonding of the subsequent brush copolymerlayer. For example, a plasma with an inert gas will also improvebonding.

The biomedical device is then subjected to a surface treatment inaccordance with the present invention. In general, the biomedical devicesuch as a wettable silicone-based hydrogel lens is contacted with asolution containing at least one or more of the brush copolymers of thepresent invention, whereby the brush copolymer forms a complex with theplurality of biomedical device surface functional groups on the surfaceof the biomedical device. The biomedical devices can either be contactedwith the solution containing at least the brush copolymers directly inthe mold assembly or the biomedical device can be released from the moldassembly and then contacted with the solution. The solutions can bewater-based solutions containing the brush copolymers and render alubricious, stable, highly wettable surface. The complexation treatmentis advantageously performed under autoclave conditions.

Another embodiment is directed to a packaging system for the storage ofan ophthalmic device comprising a sealed container containing one ormore unused ophthalmic devices immersed in an aqueous packaging solutioncomprising one or more brush copolymers comprising (a) monomeric unitsderived from an ethylenically unsaturated-containing monomer containingone or more boronic acid moieties; and (b) monomeric units derived froman ethylenically unsaturated-containing macromonomer having hydrophilicunits and boronic acid units, wherein the solution has an osmolality ofat least about 200 mOsm/kg, a pH of about 6 to about 9 and is heatsterilized. The amount of the brush copolymer employed in a packagingsolution for storing an ophthalmic device in a packaging system of thepresent invention is an amount effective to improve the surfaceproperties of the ophthalmic device. Generally, the concentration of abrush copolymer present in the packaging solution of the invention willrange from about 0.01 to about 10% w/w.

The packaging solutions according to the present invention arephysiologically compatible. Specifically, the solution must be“ophthalmically safe” for use with a lens such as a contact lens,meaning that a contact lens treated with the solution is generallysuitable and safe for direct placement on the eye without rinsing, thatis, the solution is safe and comfortable for daily contact with the eyevia a contact lens that has been wetted with the solution. Anophthalmically safe solution has a tonicity and pH that is compatiblewith the eye and includes materials, and amounts thereof, that arenon-cytotoxic according to ISO standards and U.S. Food & DrugAdministration (FDA) regulations.

The packaging solution should also be sterile in that the absence ofmicrobial contaminants in the product prior to release must bestatistically demonstrated to the degree necessary for such products.The liquid media useful in the present invention are selected to have nosubstantial detrimental effect on the lens being treated or cared forand to allow or even facilitate the present lens treatment ortreatments. The liquid media are preferably aqueous-based. Aparticularly useful aqueous liquid medium is that derived from saline,for example, a conventional saline solution or a conventional bufferedsaline solution.

The pH of the present solutions should be maintained within the range ofabout 6 to about 9, and preferably about 6.5 to about 7.8. Suitablebuffers may be added, such as boric acid, sodium borate, potassiumcitrate, citric acid, sodium bicarbonate, TRIS and various mixedphosphate buffers (including combinations of Na₂HPO₄, NaH₂PO₄ andKH₂PO4) and mixtures thereof. Generally, buffers will be used in amountsranging from about 0.05 to about 2.5 percent by weight, and preferablyfrom about 0.1 to about 1.5 percent by weight of the solution. Thepackaging solutions of this invention preferably contain a boratebuffer, containing one or more of boric acid, sodium borate, potassiumtetraborate, potassium metaborate or mixtures of the same.

Typically, the solutions of the present invention are also adjusted withtonicity agents, to approximate the osmotic pressure of normal lacrimalfluids which is equivalent to a 0.9 percent solution of sodium chlorideor 2.5 percent of glycerol solution. The solutions are madesubstantially isotonic with physiological saline used alone or incombination, otherwise if simply blended with sterile water and madehypotonic or made hypertonic the lenses will lose their desirableoptical parameters. Correspondingly, excess saline may result in theformation of a hypertonic solution which will cause stinging and eyeirritation.

Examples of suitable tonicity adjusting agents include, but are notlimited to, sodium and potassium chloride, dextrose, glycerin, calciumand magnesium chloride and the like and mixtures thereof. These agentsare typically used individually in amounts ranging from about 0.01 toabout 2.5% w/v and preferably from about 0.2 to about 1.5% w/v.Preferably, the tonicity agent will be employed in an amount to providea final osmotic value of at least about 200 mOsm/kg, preferably fromabout 200 to about 400 mOsm/kg, more preferably from about 250 to about350 mOsm/kg, and most preferably from about 280 to about 320 mOsm/kg.

If desired, one or more additional components can be included in thepackaging solution. Such additional component or components are chosento impart or provide at least one beneficial or desired property to thepackaging solution. Such additional components may be selected fromcomponents which are conventionally used in one or more ophthalmicdevice care compositions. Examples of such additional components includecleaning agents, wetting agents, nutrient agents, sequestering agents,viscosity builders, contact lens conditioning agents, antioxidants, andthe like and mixtures thereof. These additional components may each beincluded in the packaging solutions in an amount effective to impart orprovide the beneficial or desired property to the packaging solutions.For example, such additional components may be included in the packagingsolutions in amounts similar to the amounts of such components used inother, e.g., conventional, contact lens care products.

Useful sequestering agents include, but are not limited to, disodiumethylene diamine tetraacetate, alkali metal hexametaphosphate, citricacid, sodium citrate and the like and mixtures thereof.

Useful viscosity builders include, but are not limited to, hydroxyethylcellulose, hydroxymethyl cellulose, polyvinyl pyrrolidone, polyvinylalcohol and the like and mixtures thereof.

Useful antioxidants include, but are not limited to, sodiummetabisulfite, sodium thiosulfate, N-acetylcysteine, butylatedhydroxyanisole, butylated hydroxytoluene and the like and mixturesthereof.

The method of packaging and storing an ophthalmic device such as acontact lens according to the present invention includes at leastpackaging an ophthalmic device immersed in the aqueous packagingsolution described above. The method may include immersing theophthalmic device in an aqueous packaging solution prior to delivery tothe customer/wearer, directly following manufacture of the contact lens.Alternately, the packaging and storing in the solution of the presentinvention may occur at an intermediate point before delivery to theultimate customer (wearer) but following manufacture and transportationof the lens in a dry state, wherein the dry lens is hydrated byimmersing the lens in the packaging solution. Consequently, a packagefor delivery to a customer may include a sealed container containing oneor more unused contact lenses immersed in an aqueous packaging solutionaccording to the present invention.

In one embodiment, the steps leading to the present ophthalmic devicepackaging system includes (1) molding an ophthalmic device in a moldcomprising at least a first and second mold portion, (2) hydrating andcleaning the device in a container comprising at least one of the moldportions, (3) introducing the packaging solution with the copolymer intothe container with the device supported therein, and (4) sealing thecontainer. Preferably, the method also includes the step of sterilizingthe contents of the container. Sterilization may take place prior to, ormost conveniently after, sealing of the container and may be effected byany suitable method known in the art, e.g., by autoclaving of the sealedcontainer at temperatures of about 120° C. or higher.

The following examples are provided to enable one skilled in the art topractice the invention and are merely illustrative of the invention. Theexamples should not be read as limiting the scope of the invention asdefined in the claims.

In the examples, the following abbreviations are used.

DMA: N,N-dimethylacrylamide

SBA: 4-vinylphenylboronic acid

DMAPMA: N-[3-(dimethylamino)propyl]methacrylamide

Vazo™ 64: azo bis-isobutylnitrile (AIBN)

EDTA: ethylenediaminetetraacetic acid

Example 1 Preparation of Methacrylated DMA/SBA Macromer

To a 1-L 3-neck round bottom flask containing a magnetic stir bar,water-cooled condenser and thermocouple was added 0.138 g AIBN (0.35-wt% based on total weight of DMA), 3.32 g (10-mol % based on DMA and SBA,Aldrich Cat. No. M2650) of 2-mercaptoethanol, 3.14 g (5-mol % based onDMA, Aldrich Cat. No. 417580) of SBA and 40.0 g of distilled DMA(Aldrich Cat. No. 274135). The mixture was dissolved by the addition of300 mL of anhydrous acetonitrile to the flask. The solution was spargedwith argon for at least 10 minutes before gradual heating to 60° C. Thesparging was discontinued when the solution reached 40 to 45° C. and theflask was subsequently maintained under argon backpressure. After 72hours heating was discontinued at which point the room temperaturesolution was added dropwise to 6 L of stirred ethyl ether. The ether wasdecanted off and the resulting solid was dried in vacuo at 85° C.overnight affording 35.1 g of hydroxyl-terminated prepolymer.

To a 1-L 3-neck round bottom flask containing a magnetic stir bar,water-cooled condenser and 125 mL addition funnel was added 15.0 g ofhydroxyl-terminated prepolymer, 250 mL of acetonitrile and 150 mL ofchloroform. The addition funnel was charged with a solution of 4.22 g (2equivalents based on hydroxyl content) of methacrylic anhydride (AldrichCat. No. 276685), 2.63 g of triethylamine (Aldrich Cat. No. 471283) and0.17 g 4-dimethylaminopyridine (Aldrich Cat. No. 522805) in 15 mL ofchloroform. The funnel contents were added dropwise to the flaskcontents heated to 60° C. and stirred overnight at that temperature.After cooling to room temperature, 30 g of Amberlite IRA-400ion-exchange resin was added and stirred for 4 hours. The ion-exchangeresin was filtered and the filtrate was concentrated to 150 mL andprecipitated into ethyl ether. The solid was redissolved in 200 mL ofchloroform and stirred over 30-g of Amberlite IRA-400 for 72 hours. Theslurry was filtered through Celite and the filtrate precipitated inethyl ether. After vacuum drying, 5.72 g of methacrylated DMA/SBAmacromer was obtained.

Example 2 Preparation of DMA/SBA Brush Polymer

To a 300-mL 3-neck round bottom flask containing a magnetic stir bar,water-cooled condenser and thermocouple was added 0.093 g AIBN (1.0-wt %based on total weight of monomers), 0.29 g (4.5-mol %, Aldrich Cat. No.417580) of SBA, 5.0 g of the methacrylated DMA/SBA macromer of Example 1(10 mol %), 0.67-g (9.0-mol %, Aldrich Cat. No. 409472-1 L) ofdeinhibited and distilled DMAPMA and 3.30-g (76.5-mol %, Aldrich Cat.No. 274135-500ML) of distilled DMA. The monomers and initiator weredissolved by addition of 100 mL of methanol to the flask. The solutionwas sparged with argon for at least 10 minutes before gradual heating to60° C. The sparging was discontinued when the solution reached 40 to 45°C. and the flask was subsequently maintained under argon backpressure.After 72 hours heating was discontinued, at which point the cooledsolution was added drop wise to 6 L of mechanically stirred ethyl ether.The precipitate was isolated by vacuum filtration. The solid was driedin vacuo at 80° C. for a minimum of 18 hours, affording 8.12 g of brushcopolymer.

Example 3

Contact lenses made of Balafilcon A were cast and processed understandard manufacturing procedures. Balafilcon A is a copolymer comprisedof 3-[tris(tri-methylsiloxy)silyl]propyl vinyl carbamate,N-vinyl-2-pyrrolidone (NVP),1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]polydimethylsiloxane andN-vinyloxycarbonyl alanine. All Balafilcon A lenses were air-plasmatreated prior to exposure to the brush copolymer coating of Example 2.

For coating with the subject brush copolymer, each lens was placed in apolypropylene blister containing 3.8-mL of a 500 ppm (w/v) solution ofthe subject polymer dissolved in borate-buffered saline (BBS) containing300 ppm EDTA. The blisters were sealed and autoclaved at 121° C. for 30minutes. Examination of thoroughly rinsed coated lenses were examined byX-ray photoelectron spectroscopy (XPS) and compared to uncoated controlslenses. The XPS results for the lenses are set forth below in Table 1.

TABLE 1 Sample % C % N % O % Si Control 64.7 ± 0.3 7.4 ± 0.2 21.0 ± 0.26.9 ± 0.2 Test 68.3 ± 0.4 8.8 ± 0.5 18.4 ± 0.4 4.5 ± 0.4

It will be understood that various modifications may be made to theembodiments disclosed herein. Therefore the above description should notbe construed as limiting, but merely as exemplifications of preferredembodiments. For example, the functions described above and implementedas the best mode for operating the present invention are forillustration purposes only. Other arrangements and methods may beimplemented by those skilled in the art without departing from the scopeand spirit of this invention. Moreover, those skilled in the art willenvision other modifications within the scope and spirit of the featuresand advantages appended hereto.

What is claimed is:
 1. A brush copolymer comprising (a) monomeric unitsderived from an ethylenically unsaturated boronic acid-containingmonomer and (b) a macromonomer having hydrophilic units and boronic acidunits, wherein the ethylenically unsaturated boronic acid-containingmonomer is derived from an ethylenically unsaturated aryl boronic acid.2. The brush copolymer of claim 1, wherein the ethylenically unsaturatedboronic acid-containing monomer is derived from moieties selected fromthe group consisting of 4-vinylphenylboronic acid,3-methacrylamidophenylboronic acid, 3-acrylamidophenylboronic acid andmixtures thereof.
 3. The brush copolymer of claim 1, wherein theethylenically unsaturated boronic acid-containing monomer furthercomprises monomeric units derived from an ethylenically unsaturatedmonomer containing a tertiary-amine moiety.
 4. The brush copolymer ofclaim 1, wherein the ethylenically unsaturated boronic acid-containingmonomer further comprises monomeric units derived from an ethylenicallyunsaturated monomer containing a hydrophilic moiety capable of renderingthe brush copolymer water-soluble.
 5. The brush copolymer of claim 4,wherein the hydrophilic moiety capable of rendering the brush copolymerwater-soluble is derived from a hydrophilic monomer selected from thegroup consisting of N-vinyl pyrrolidone, N-vinyl-N-methyl acetamide,N,N-dimethyl methacrylamide, N,N-dimethylacrylamide, and mixturesthereof.
 6. The brush copolymer of claim 3, comprising about 1 to about20 mole percent of the ethylenically unsaturated boronic acid-containingmonomeric units, about 1 to about 20 mole percent of the macromonomerhaving hydrophilic units and boronic acid units, about 1 to about 20mole percent of monomeric units derived from an ethylenicallyunsaturated monomer containing a tertiary-amine moiety, and about 40 toabout 90 mole percent of monomeric units derived from an ethylenicallyunsaturated monomer containing a hydrophilic moiety capable of renderingthe brush copolymer water-soluble.
 7. A biomedical device having acoating on a surface thereof, the coating comprising the brush copolymerof claim 1, wherein the ethylenically unsaturated boronicacid-containing monomer is derived from an ethylenically unsaturatedaryl boronic acid.
 8. A biomedical device having a coating on a surfacethereof, the coating comprising the brush copolymer of claim 1, whereinthe ethylenically unsaturated boronic acid-containing monomer is derivedfrom one or more moieties selected from the group consisting of4-vinylphenylboronic acid, 3-methacrylamidophenylboronic acid,3-acrylamidophenylboronic acid and mixtures thereof.
 9. A biomedicaldevice having a coating on a surface thereof, the coating comprising thebrush copolymer of claim 1, wherein the brush copolymer furthercomprises monomeric units derived from an ethylenically unsaturatedmonomer containing a hydrophilic moiety capable of rendering the brushcopolymer water-soluble, and further wherein the hydrophilic moietycapable of rendering the brush copolymer water-soluble is derived from ahydrophilic monomer selected from the group consisting of N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, N,N-dimethyl methacrylamide,N,N-dimethylacrylamide, and mixtures thereof.